Utilization of derivatives of 2,5-dihydroxyphenylcarboxylic acids, their homologs, and their salts in preparation of a cosmetic or dermatological composition with a depigmenting action

ABSTRACT

A cosmetic or dermatological composition with a depigmenting action comprises derivatives of 2,5-dihydroxyphenylcarboxylic acids, their homologs, and their salts, with the derivatives having the following structural formula: ##STR1## wherein: R 1  represents OR 5 , OH, or ##STR2## R 5  is a linear or branched C 1  -C 20  alkyl radical, a linear or branched C 2  -C 20  alkenyl radical, or a C 1  -C 20  alkyl radical substituted by one or more hydroxy or alkoxy groups; 
     r&#39; and r&#34;, identical or different, represent a hydrogen atom, a C 1  -C 20  alkyl radical, a C 2  -C 6  hydroxyalkyl radical, or a C 3  -C 6  polyhydroxyalkyl, or r&#39; and r&#34; taken together, with the nitrogen atom, form a heterocycle; 
     the number of carbon atoms in the --(CH 2 ) n  --COR 1  chain is less than or equal to 21; 
     R 2  and R 3 , identical or different, represent a hydrogen atom, a linear or branched C 1  -C 4  alkyl radical, or a C 1  -C 4  alkoxy; 
     R 4  represents a hydrogen atom or a linear or branched C 1  -C 4  alkyl radical; and 
     n is an integer from 0 to 20, provided that, when R 2  and R 3  represent a hydrogen atom, n is greater than or equal to 2.

This is a division of application Ser. No. 07/913,950 filed Jul. 17, 1992 now U.S. Pat. No. 5,449,518.

The present invention relates to the use of derivatives of 2,5-dihydroxyphenylcarboxylic acids, their homologs, and their salts for the preparation of cosmetic or dermatological compositions which when topically applied, bleach the skin or treat pigmented spots. The invention also relates to novel homologs of 2,5-dihydroxyphenylcarboxylic acid.

BACKGROUND

The mechanism by which skin pigmentation is formed, namely by which melanins are formed, is particularly complex and schematically involves the following main steps: ##STR3## with the enzyme involved in this series of reactions being essentially tyrosinase.

The substances in widest use at the present time as depigmentors are in particular hydroquinone and its derivatives, particularly its ethers such as hydroquinone monomethyl ether.

These compounds, while they are definitely effective, are unfortunately not bereft of side effects, which can make their use delicate or even dangerous.

Thus, hydroquinone, whose use is moreover limited to a concentration of 2%, is a compound that is particularly irritating and cytotoxic to the melanocyte, and whose total or partial replacement has been considered by many authors.

Thus, U.S. Pat. No. 4,526,779 has proposed certain hydroquinone fatty esters that have good activity and are less irritating and more stable than hydroquinone.

Likewise, other hydroquinone derivatives that do not have the drawbacks of hydroquinone but whose efficacy has proved relatively poor have been proposed in Japanese Patent Application No. 27909/86.

It is well established that a substance has a depigmenting effect if it acts directly on the vitality of the epidermal melanocytes where melanogenesis normally occurs and/or if it interferes with one of the stages in melanin biosynthesis, either by inhibiting one of the enzymes involved or by intercalation as a structural analog in the synthesis pathway which can accordingly be blocked, hence the depigmenting effect.

The use of topical depigmentors that have good efficacy and are harmless is particularly desirable with a view to treating regional hyperpigmentation caused by melanocytic hyperactivity such as idiopathic melasma occurring during pregnancy (mask of pregnancy or chloasma) or secondary to estrogen-progesterone contraception; local hyperpigmentation caused by benign melanocytic hyperactivity and proliferation such as lentigo senilis, or liver spots; accidental hyperpigmentation such as postlesional photosensitization and scarring; and certain forms of leukoderma such as vitiligo where, if the injured skin cannot be repigmented, the residual zones of normal skin are depigmented to impart a homogeneous white color to the entire skin.

SUMMARY OF THE INVENTION

After numerous studies on a number of substances, it has surprisingly been found that certain 2,5-dihydroxyphenylcarboxylic acid derivatives, their homologs, and their salts have particularly pronounced depigmenting action which is distinctly superior to that of hydroquinone in an in vitro tyrosinase activity inhibition test.

Hence, an object of the present invention is the use of derivatives of 2,5-dihydroxyphenylcarboxylic acids, their homologs, and their salts for preparing a cosmetic or dermatological composition with a depigmenting action, said derivatives having the following structural formula: ##STR4## wherein: R₁ represents OR₅, OH, or ##STR5## R₅ is a linear or branched C₁ -C₂₀ alkyl radical, a linear or branched C₂ -C₂₀ alkenyl radical, or a C₁ -C₂₀ alkyl radical substituted by one or more hydroxy or alkoxy groups;

r' and r", identical or different, represent a hydrogen atom, a C₁ -C₂₀ alkyl radical, a C₂ -C₆ hydroxyalkyl radical, or a C₃ -C₆ polyhydroxyalkyl, or r' and r" taken together, with the nitrogen atom, form a heterocycle;

the number of carbon atoms in the --(CH₂)_(n) --COR₁ chain is less than or equal to 21;

R₂ and R₃, identical or different, represent a hydrogen atom, a linear or branched C₁ -C₄ alkyl radical, or a C₁ -C₄ alkoxy;

R₄ represents a hydrogen atom or a linear or branched C₁ -C₄ alkyl radical; and

n is an integer from 0 to 20, provided that, when R₂ and R₃ represent a hydrogen atom, n is greater than or equal to 2.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

According to a preferred embodiment of the invention, examples of a suitable C₁ -C₂₀ alkyl radical include a methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, isoamyl, octyl, 2-ethylhexyl, dodecyl, tetradecyl, hexadecyl, or octadecyl radical.

An example of a suitable C₂ -C₂₀ alkenyl radical is the oleyl radical.

An example of a suitable C₁ -C₂₀ alkyl radical substituted by one or more hydroxy or alkoxy groups is a hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl, methoxyethyl, or ethoxymethyl radical.

An example of a suitable C₂ -C₆ hydroxyalkyl radical is a 2-hydroxyethyl, 2-hydroxypropyl, or 3-hydroxypropyl radical.

An example of a suitable C₃ -C₆ polyhydroxyalkyl radical is a radical having 3 to 6 carbon atoms and 2 to 5 hydroxyl groups such as the 2,3-dihydroxypropyl, 2,3,4-trihydroxybutyl, or 2,3,4,5-tetrahydroxypentyl radical.

An example of a suitable C₁ -C₄ alkoxy radical is a methoxy, ethoxy, propoxy, isopropoxy, or butoxy radical.

When r' and r" taken together form a heterocycle with the nitrogen atom, this can be a morpholino, pyrrolidino, piperidino, piperazino ring, or piperazino ring substituted by C₁ -C₄ alkyl or C₂ -C₆ hydroxyalkyl.

The 2,5-dihydroxyphenylcarboxylic acid derivatives with structural formula (I) are known for the most part and have been described in French Patents Nos. 7824174 (U.S. Pat. No. 2,400,358) and 7824175 (U.S. Pat. No. 2,400,359).

Examples of compounds with general formula (I) include the following:

2,5-dihydroxyphenylpropionic acid and its ethyl and lauric esters,

2,5-dihydroxy-3,4-dimethylphenylacetic acid and its ethyl ester,

methyl 2,5-dihydroxy-4-methylphenylacetate,

2,5-dihydroxy-4-methylphenylacetic acid,

2,5-dihydroxy-4-methylphenylpropionic acid and its ethyl ester,

2,5-dihydroxy-4-methylbenzoic acid and its methyl or ethyl ester,

2,5-dihydroxy-4-ethylbenzoic acid,

2,5-dihydroxy-4-methoxybenzoic acid and its methyl ester,

2,5-dihydroxy-4-ethoxybenzoic acid,

3-(2,5-dihydroxy-4'-methylphenyl)-1-N(ω-carboxydecyl) propylamide,

2,5-dihydroxy-4-methylphenylbutanoic acid,

2,5-dihydroxy-4-methylphenylhexanoic acid,

2,5-dihydroxy-4-methoxyphenylacetic acid and its methyl ester,

2,5-dihydroxy-4-methoxyphenylacetamide,

methyl ester of 2,5-dihydroxy-3-methoxyphenylacetic acid,

2,5-dihydroxy-3-methoxyphenylpentadecanoic acid and its methyl ester,

2,5-dihydroxyphenylbutanoic acid and its methyl ester,

2,5-dihydroxyphenylbutylamide,

2,5-dihydroxyphenylpentanoic acid,

2,5-dihydroxyphenylpentylamide,

2,5-dihydroxyphenylhexanoic acid,

2,5-dihydroxyphenyloctanoic acid,

2,5-dihydroxyphenyldecanoic acid and its ethyl ester,

2,5-dihydroxyphenylundecanoic acid and its methyl ester,

2,5-dihydroxy-3,4-dimethylphenylbutanoic acid,

2,5-dihydroxy-3,4-dimethoxyphenylacetic acid,

ethyl ester of 2,5-dihydroxy-4,6-dimethylphenylacetic acid,

2-(2,5-dihydroxy-4-methylphenyl)-N-octylacetamide, and

6-(2,5-dihydroxy-4-methoxyphenyl)hexanoic acid.

According to a preferred embodiment of the invention, the derivatives of 2,5-dihydroxyphenylcarboxylic acids, their homologs, and their salts have the following general formula (II): ##STR6## wherein: R'₁ has the same meaning as given hereinabove for R₁ according to formula (I);

m is 1 or 2;

(i) when m is 1, at least one of the radicals R'₂ and R'₃ represents a linear or branched C₁ -C₄ alkyl radical, and the other can represent a hydrogen atom, and

(ii) when m is 2, R'₂ and R'₃, which are identical or different, represent a hydrogen atom or a linear or branched C₁ -C₄ alkyl radical.

Examples of compounds with general formula (II) include the following:

2,5-dihydroxyphenylpropionic acid,

2,5-dihydroxy-3,4-dimethylphenylacetic acid,

methyl 2,5-dihydroxy-4-methylphenylacetate,

2,5-dihydroxy-4-methylphenylacetic acid, and

2,5-dihydroxy-4-methylphenylpropionic acid.

In the depigmenting compositions according to the present invention, the concentration of 2,5-dihydroxyphenylcarboxylic acid derivatives, homologs, and salts with formula (I) is generally between 0.01 and 10%, and preferably between 0.5 and 5 wt. %, relative to the total weight of the composition.

Examples of vehicles for application of the compositions include an aqueous or water-alcohol solution, an emulsion of the oil-in-water or water-in-oil type, an emulsified gel, or a two-phase system.

Preferably, the compositions according to the invention are in the form of a lotion, a cream, a milk, a gel, a mask, microspheres or nanospheres, or vesicular dispersions. In the case of vesicular dispersions, the lipids of which the vesicles are made can be of the ionic or nonionic type, or a mixture thereof.

These cosmetic compositions can optionally also contain a moistener, a surfactant, a keratolytic, an anti-inflammatory agent, a complexing agent, an antioxidant, a preservative, a fragrance, or a sunscreen.

These compositions are applied topically in an amount corresponding to the conventional application doses for the type of composition in question (gel, cream, lotion, etc.). For example, in the case of a cream, 0.5 to 3 mg is used, and in particular 1 to 2 mg of cream per cm² of skin per application, at the rate of one or two applications per day.

The present invention also has as an object novel compounds which are derivatives of 2,5-dihydroxyphenylcarboxylic acid having the following structural formula (III): ##STR7## wherein: R represents the OR' or NHR" radical, R' represents a linear or branched C₁ -C₆ lower alkyl radical, and R" represents a C₄ -C₁₂ alkyl radical.

Examples of compounds with formula (III) include the following:

methyl 2,5-dihydroxy-4-methylphenylacetate,

ethyl 2,5-dihydroxy-4-methylphenylacetate,

propyl 2,5-dihydroxy-4-methylphenylacetate,

isopropyl 2,5-dihydroxy-4-methylphenylacetate,

butyl 2,5-dihydroxy-4-methylphenylacetate,

isoamyl 2,5-dihydroxy-4-methylphenylacetate, and

N-octyl-2-(2,5-dihydroxy-4-methylphenyl)acetamide.

In vitro Studies

Certain of the 2,5-dihydroxyphenylcarboxylic acid derivatives, their homologs, and their salts with general formula (I) have been studied by comparison to hydroquinone in equivalent molar quantities in the in vitro tyrosinase activity inhibition test.

According to this test, the quantity of dopachrome formed during the chain of reactions by which tyrosine is converted into melanins is monitored by visible spectrometry at 475 nm. These reactions are catalyzed in vitro by fungal tyrosinase in the presence of a reducing cosubstrate (for example L-dopa in a small quantity) to initiate the hydroxylation reaction of L-tyrosine into L-dopa. The L-dopa is then oxidized catalytically into dopaquinone and then into dopachrome, an intermediate formed prior to the nonenzymatic oxidation reactions that lead to formation of melanins.

Hence, the concentration of dopachrome formed over time both in the presence and in the absence of the inhibitor is measured.

The inhibitor concentrations are established at 50 mol. % relative to the tyrosine concentration in the reaction medium.

The effect of inhibition is expressed by the decrease in the maximum quantity of dopachrome formed (optical density value at 475 nm read from the plateau of the curve) relative to the quantity obtained in the absence of inhibitor.

Experimental Conditions Reagents

A--0.1 M phosphate buffer, pH=6.5 (Tween 20, 1%)

B--Stock solution of L-tyrosine, 2×10⁻³ M in A

C--Stock solution of L-dopa, 10⁻⁴ M in A

D--Stock solution of fungal tyrosinase, 2400 units/ml, in A

E--Stock solution of inhibitor, 10⁻² M in A (solutions C and D must be prepared on the day of the experiment).

Results

reference cell: 3 ml of A

test cell:

1 ml of B

0.1 ml of C

1.85 ml of A+E

homogenize and equilibrate at 25° C.

add 0.05 ml of D

mix rapidly and observe kinetics by measuring absorbance at 475 nm as a function of time.

                  TABLE I                                                          ______________________________________                                         Compounds              % Inhibition                                            ______________________________________                                          ##STR8##              -87%                                                     ##STR9##              -66%                                                     ##STR10##             -59%                                                     ##STR11##             -64%                                                     ##STR12##             -42%                                                     ##STR13##             -33%                                                    ______________________________________                                    

As illustrated in Table 1, the 2,5-dihydroxyphenylcarboxylic acid derivatives, their homologs, and their salts of the compositions according to the present invention have melanogenesis-inhibiting activity distinctly superior to that of hydroquinone.

PREPARATION EXAMPLES Example I Preparation of methyl 2,5-dihydroxy-4-methylphenylacetate

A mixture of 145.6 g of 2,5-dihydroxy-4-methylphenylacetic acid and 45 g of dry sulfonic acid resin (IRN-77^(R)) is heated under reflux in 4.38 liters of absolute methanol. The mixture is filtered and the filtrate evaporated. The white solid is recrystallized from a mixture of ethyl acetate and heptane (50:50), yielding white crystals with the following characteristics:

Melting point=138.5° C.

Elementary analysis:

Calculated: C% 61.22, H% 6.16, O% 32.62.

Actual: C% 61.23, H% 6.14, O% 32.40.

Examples 2 to 6

Using the method described above for Example 1 but replacing the ethanol by the corresponding alcohol, the following compounds were prepared:

Example 2 ethyl 2,5-dihydroxy-4-methylphenylacetate

White crystals, m.p.=134° C. (isopropyl acetate)

Elementary analysis: C₁₁ H₁₄ O₄ :

Calculated: C% 62.85, H% 6.71, O% 30.44.

Actual: C% 62.79, H% 6.72, O% 30.32.

Example 3 propyl 2,5-dihydroxy-4-methylphenylacetate

White crystals, m.p.=101° C. (isopropyl ether)

Elementary analysis: C₁₂ H₁₆ O₄ :

Calculated: C% 64.27, H% 7.19, O% 28.54.

Actual: C% 64.32, H% 7.22, O% 28.45.

Example 4 isopropyl 2,5-dihydroxy-4-methylphenylacetate

White crystals, m.p.=123° C. (water)

Elementary analysis: C₁₂ H₁₆ O₄ :

Calculated: C% 64.27, H% 7.19, O% 28.54.

Actual: C% 64.13, H% 7.28, O% 28.34.

Example 5 butyl 2,5-dihydroxy-4-methylphenylacetate

White crystals, m.p.=113° C. (water)

Elementary analysis: C₁₃ H₁₈ O₄ :

Calculated: C% 65.53, H% 7.61, O% 26.86.

Actual: C% 65.58, H% 7.60, O% 27.02.

Example 6 isoamyl 2,5-dihydroxy-4-methylphenylacetate

White crystals, m.p.=99° C. (isopropyl acetate)

Elementary analysis for C₁₄ H₂₀ O₄ :

Calculated: C% 66.65, H% 7.99, O% 25.36.

Actual: C% 66.47, H% 7.91, O% 25.09.

Example 7 Preparation of N-octyl-(2,5-dihydroxy-4-methylphenyl)-acetamide

A solution of 7.75 g of n-octylamine dissolved in 15 ml of dimethylformamide is placed in a solution of 10 g of 5-hydroxy-6-methyl-3H-benzofuran-2-one dissolved in 15 ml of dimethylformamide. After 15 minutes at 100° C., the mixture is evaporated to dryness at reduced pressure. It is treated with 100 ml of ethyl acetate, rinsed with water, dried, then evaporated, yielding a white solid which is recrystallized from isopropyl acetate.

Melting point: 118° C. white crystals

Elementary analysis: C₁₇ H₂₇ NO₃ :

Calculated: C% 69.59, H% 9.28, N% 4.77, O% 16.36.

Actual: C% 69 50, H% 9.15, N% 4.58, O% 16.66.

Example 8 Preparation of 6-(2,5-dihydroxy-4-methoxyphenyl)-hexanoic acid a) Preparation of 6-(2,5-dihydroxy-4-methoxyhenyl)-6-oxohexanoic acid

Seven grams of 2-methoxyhydroquinone and 13.6 g of the monomethyl ester of adipic acid in 60 ml of dichloroethane are mixed under nitrogen in a three-necked flask. Thirteen milliliters of boron trifluoride etherate is run in at room temperature. After five hours of refluxing, the reaction medium is poured into a mixture of 40 g of sodium acetate trihydrate and 100 ml of water. The product is extracted with 500 ml of ethyl acetate, washed, dried, and concentrated under vacuum. The residue is treated with a mixture of 1.4 ml of concentrated sulfuric acid, 14 ml of water, and 40 ml of acetic acid at 80° C. for three hours, then the solution is poured into 100 ml of ice water. The precipitate is filtered, washed several times with 20 ml of water, and dried. The solid is recrystallized from a mixture of ethyl acetate and isopropyl ether, yielding yellow crystals with the following characteristics:

Melting point: 165° C.

Elementary analysis: C₁₃ H₁₆ O₆ :

Calculated: C% 58.20, H% 6.01, O% 35.78.

Actual: C% 58.02, H% 6.09, O% 35.73.

b) Preparation of 6-(2,5-dihydroxy-4-methoxyphenyl)-hexanoic acid

Two grams of mossy zinc, 0.13 g of mercuric chloride, 0.13 ml of concentrated hydrochloric acid, and 4 ml of water are mixed while stirring. After ten minutes the aqueous phase is decanted, then the amalgam is rinsed with water. To this amalgam are added a solution of 2.5 g of 6-(2,5-dihydroxy-4-methoxyphenyl)-6-oxohexanoic acid in 20 ml of toluene, then a dilute hydrochloric acid solution (6 ml concentrated HCl and 3 ml of water). After eight hours of refluxing, the solution is poured into 300 ml of ice water. The desired compound is extracted with ethyl acetate (3×100 ml) and washed with water, dried, then evaporated under vacuum. The solid is recrystallized from a mixture of ethyl acetate and heptane to give white crystals with the following characteristics:

Melting point: 142° C.

Elementary analysis: C₁₃ H₁₈ O₅ :

Calculated: C% 61.41, H% 7.14, O% 31.46.

Actual: C% 61.33, H% 7.20, O% 31.50.

EXAMPLES OF COMPOSITIONS Example 1 Water-in-oil emulsion

    ______________________________________                                         Glycerin                   5       g                                           Propylene glycol           10      g                                           Methyl 2,5-dihydroxy-4-methylphenylacetate                                                                0.5     g                                           Cyclomethicone (cyclopentadimethylsiloxane)                                                               20      g                                           Abil WO9 (mixture of ethoxylated propoxylated                                                             3       g                                           polycetyldimethylsiloxane, polyglyceryl isostearate                            with 4 mols of glycerin, and hexyl laurate)                                    Fragrance                  0.1     g                                           Preservatives              0.2     g                                           Water                      qs. 100 g                                           ______________________________________                                    

In this example, the methyl 2,5-dihydroxy-4-methylphenylacetate can advantageously be replaced by 0.8 g of 2,5-dihydroxy-4-methylphenylhexanoic acid.

Example 2 Water-in-oil emulsion

    ______________________________________                                         Propylene glycol         11       g                                            Methyl 2,5-dihydroxy-4-methylphenylacetate                                                              0.5      g                                            Mineral oil (vaseline)   20.5     g                                            Sorbitan isostearate (fatty acid esters and                                                             5        g                                            sorbitol)                                                                      Miglycol Gel B (hectorite modified by                                                                   5        g                                            dimethylbenzylstearylammonium chloride in                                      glyceryl dicaprylate/dicaprate)                                                Coco-caprylate/caprate (esters of C.sub.8 -C.sub.10 acids                                               1        g                                            and C.sub.12 -C.sub.18 fatty alcohol)                                          Fragrance                0.1      g                                            Preservatives            0.2      g                                            Water                    qs. 100  g                                            ______________________________________                                    

In this example, the methyl 2,5-dihydroxy-4-methylphenylacetate can be replaced by 0.8 g of isoamyl 2,5-dihydroxy-4-methylphenylacetate.

Example 3 Oil-in-water emulsion

    ______________________________________                                         Ceteareth 20 (cetylstearyl alcohol ethoxylated with                                                       1       g                                           20 moles of ethylene oxide)                                                    Glycol stearate (ethylene glycol palmitostearate)                                                         3       g                                           Coco-caprylate/caprate (esters of C.sub.8 -C.sub.10                                                       5       g                                           acids and C.sub.12 -C.sub.18 fatty alcohol)                                    Carbomer 934 (carboxyvinyl polymer)                                                                       0.3     g                                           Triethanolamine            0.9     g                                           96% Ethyl alcohol          20      g                                           Methyl 2,5-dihydroxy-4-methylphenylacetate                                                                1.5     g                                           Glycerin                   3       g                                           Fragrance                  0.1     g                                           Preservatives              0.2     g                                           Water                      qs. 100 g                                           ______________________________________                                    

In this example, the methyl 2,5-dihydroxy-4-methylphenylacetate can be replaced by 1 g of isopropyl 2,5-dihydroxy-4-methylphenylacetate.

Example 4 Lotion

    ______________________________________                                         96% Ethyl alcohol        50       g                                            PEG (8 mols) (polyethylene glycol No. 8)                                                                30       g                                            Ethoxydiglycol           5        g                                            Glycerin                 5        g                                            Methyl 2,5-dihydroxy-4-methylphenylacetate                                                              3.6      g                                            Water                    qs. 100  g                                            ______________________________________                                    

In this example, the methyl 2,5-dihydroxy-4-methylphenylacetate can be replaced by 2.5 g of 6-(2,5-dihydroxy-4-methoxyphenyl)hexanoic acid.

While the present invention has been disclosed in connection with preferred embodiments thereof, it should be appreciated that there are other embodiments of the present invention which fall within the spirit and scope of the present invention as defined by the appended claims. 

What is claimed is:
 1. A cosmetic or dermatological composition with a depigmenting action consisting essentially of a cosmetically or dermatologically suitable carrier, 2,5-dihydroxyphenylcarboxylic acid derivatives or their cosmetically or dermatologically acceptable salts, and at least one ingredient selected from the group consisting of moisteners, surfactants, keratolytics, anti-inflammatory agents, complexing agents, antioxidants, preservatives, fragrances and sunscreens, said 2,5-dihydroxyphenylcarboxylic acid derivatives having the following structural formula: ##STR14## wherein: R₁ represents OR₅ or OH and R₅ represents a linear or branched C₁ -C₂₀ alkyl radical, a linear or branched C₂ -C₂₀ alkenyl radical, or a C₁ -C₂₀ alkyl radical substituted by one or more hydroxy or alkoxy groups,the number of carbon atoms in the (CH₂)_(n) --COR₁ chain is less than or equal to 21, R₂ and R₃, identical or different, represent a hydrogen atom, a linear or branched C₁ -C₄ alkyl radical, or a C₁ -C₄ alkoxy, R₄ represents a hydrogen atom or a linear or branched C₁ -C₄ alkyl radical, and n is an integer from 0 to 20, provided that, when R₂ and R₃ represent a hydrogen atom, n is greater than or equal to
 2. 2. A composition according to claim 1, wherein the derivatives or salts have the following formula: ##STR15## wherein R'₁ represents OR₅ or OH and R₅ represents a linear or branched C₁ -C₂₀ alkyl radical, a linear or branched C₂ -C₂₀ alkenyl radical, or a C₁ -C₂₀ alkyl radical substituted by one or more hydroxy or alkoxy groups,m is 1 or 2, and when m is 1, at least one of the radicals R'₂ and R'₃ represents a linear or branched C₁ -C₄ alkyl radical, and the other can represent a hydrogen atom, and when m is 2, R'₂ and R'₃, which are identical or different, represent a hydrogen atom or a linear or branched C₁ -C₄ alkyl radical.
 3. A composition according to claim 1, wherein the derivatives or salts are selected from the group consisting of:2,5-dihydroxyphenyl-3-propionic acid, ethyl 2,5-dihydroxyphenyl-3-propionate, lauryl 2,5-dihydroxyphenyl-3-propionate, 2,5-dihydroxy-3,4-dimethylphenylacetic acid, ethyl 2,5-dihydroxy-3,4-dimethylphenylacetate, methyl 2,5-dihydroxy-4-methylphenylacetate, 2,5-dihydroxy-4-methylphenylacetic acid, 2,5-dihydroxy-4-methylphenyl-3-propionic acid, ethyl 2,5-dihydroxy-4-methylphenyl-3-propionate,
 2. 5-dihydroxy-4-methylbenzoic acid,methyl 2,5-dihydroxy-4-methylbenzoate, ethyl 2,5-dihydroxy-4-methylbenzoate, 2,5-dihydroxy-4-ethylbenzoic acid, 2,5-dihydroxy-4-methoxybenzoic acid, methyl 2,5-dihydroxy-4-methoxybenzoate, 2,5-dihydroxy-4-ethoxybenzoic acid, 2,5-dihydroxy-4-methylphenyl-4-butanoic acid, 2,5-dihydroxy-4-methoxyphenylacetic acid, methyl 2,5-dihydroxy-4-methoxyphenylacetate, methyl 2,5-dihydroxy-3-methoxyphenylacetate, 2,5-dihydroxy-3-methoxyphenyl-15-pentadecanoic acid, methyl 2,5-dihydroxy-3-methoxyphenyl-1,5-pentadecanoate, 2,5-dihydroxyphenyl-4-butanoic acid, methyl 2,5-dihydroxyphenyl-5-pentanoate, 2,5-dihydroxyphenyl-5-pentanoic acid, 2,5-dihydroxyphenyl-6-hexanoic acid, 2,5-dihydroxyphenyl-8-octanoic acid, 2,5-dihydroxyphenyl-10-decanoic acid, ethyl 2,5-dihydroxyphenyl-10-decanoate, 2,5-dihydroxyphenyl-11-undecanoic acid, methyl 2,5-dihydroxyphenyl-11-undecanoate, 2,5-dihydroxy-3,4-dimethylphenyl-4-butanoic acid, 2,5-dihydroxy-3,4-dimethoxyphenylacetic acid, ethyl 2,5-dihydroxy-4,6-dimethylphenylacetate, 6-(2,5-dihydroxy-4-methoxyphenyl) hexanoic acid, and their pharmaceutically or cosmetically acceptable salts.
 4. A composition according to claim 1, wherein the concentration of said derivatives or salts is between 0.01 and 10 wt %, relative to the total weight of the composition.
 5. A composition according to claim 1, wherein the concentration of said derivatives or salts is between 0.05 and 5 wt. %, relative to the total weight of the composition.
 6. A composition according to claim 1, wherein the composition is in a form selected from the group consisting of gels, masks, microspheres, nanospheres, and vesicular dispersions.
 7. A cosmetic or dermatological composition with a depigmenting action consisting essentially of(i) a cosmetically or dermatologically suitable carrier, (ii) 2,5-dihydroxyphenylcarboxylic acid derivatives or their cosmetically or dermatologically acceptable salts, having the following structural formula: ##STR16## wherein: R₁ represents OR₅ or OH and R₅ represents a linear or branched C₁ -C₂₀ alkyl radical, a linear or branched C₂ -C₂₀ alkenyl radical, or a C₁ -C₂₀ alkyl radical substituted by one or more hydroxy or alkoxy groups,the number of carbon atoms in the (CH₂)_(n) --COR₁ chain is less than or equal to 21, R₂ and R₃, identical or different, represent a hydrogen atom, a linear or branched C₁ -C₄ alkyl radical, or a C₁ -C₄ alkoxy, R₄ represents a hydrogen atom or a linear or branched C₁ -C₄ alkyl radical, and n is an integer from 0 to 20, provided that, when R₂ and R₃ represent a hydrogen atom, n is greater than or equal to 2, and (iii) at least one member selected from the group consisting of moisteners, keratolytics, anti-inflammatory agents, preservatives and sunscreens.
 8. A cosmetic or dermatological composition with a depigmenting action consisting essentially of a cosmetically or dermatologically suitable carrier and 2,5-dihydroxyphenylcarboxylic acid derivatives or their cosmetically or dermatologically acceptable salts, having the following structural formula: ##STR17## wherein: R₁ represents OR₅ or OH and R₅ represents a linear or branched C₁ -C₂₀ alkyl radical, a linear or branched C₂ -C₂₀ alkenyl radical, or a C₁ -C₂₀ alkyl radical substituted by one or more hydroxy or alkoxy groups,the number of carbon atoms in the (CH₂)_(n) --COR₁ chain is less than or equal to 21, R₂ and R₃, identical or different, represent a hydrogen atom, a linear or branched C₁ -C₄ alkyl radical, or a C₁ -C₄ alkoxy, R₄ represents a hydrogen atom or a linear or branched C₁ -C₄ alkyl radical, and n is an integer from 0 to 20, provided that, when R₂ and R₃ represent a hydrogen atom, n is greater than or equal to 2; said composition being in a form selected from the group consisting of masks, microspheres, nanospheres or vesicular dispersions. 